[3-[(allylmethylamino)methyl]-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(5-allyloxymethylfuran-2-yl)pyrimidin-2-yl]amine | 1364123-96-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [3-[(allylmethylamino)methyl]-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(5-allyloxymethylfuran-2-yl)pyrimidin-2-yl]amine
• 英文别名: N-[3-[[methyl(prop-2-enyl)amino]methyl]-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4-[5-(prop-2-enoxymethyl)furan-2-yl]pyrimidin-2-amine
• CAS: 1364123-96-5
• 化学式: C₂₉H₃₇N₅O₃
• 分子量: 503.644
• InChiKey: WWTMVHMOPLCTOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [3-[(allylmethylamino)methyl]-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(5-allyloxymethylfuran-2-yl)pyrimidin-2-yl]amine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以55%的产率得到12-methyl-15-(2-(pyrrolidin-1-yl)ethoxy)-7,25-dioxa-12,19,21,24-tetraazatetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis

  摘要：

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.

  DOI：

  10.1021/jm201454n
• 作为产物：
  描述：

  allylmethyl-[2-(2-chloroethoxy)-5-nitrobenzyl]amine 在 盐酸 、 tin(II) chloride dihdyrate 、 水 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 正丁醇 为溶剂， 反应 32.0h， 生成 [3-[(allylmethylamino)methyl]-4-(2-pyrrolidin-1-ylethoxy)phenyl]-[4-(5-allyloxymethylfuran-2-yl)pyrimidin-2-yl]amine
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis

  摘要：

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.

  DOI：

  10.1021/jm201454n

文献信息

• Discovery of the Macrocycle (9<i>E</i>)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis
  作者：Anthony D. William、Angeline C.-H. Lee、Anders Poulsen、Kee Chuan Goh、Babita Madan、Stefan Hart、Evelyn Tan、Haishan Wang、Harish Nagaraj、Dizhong Chen、Chai Ping Lee、Eric T. Sun、Ramesh Jayaraman、Mohammad Khalid Pasha、Kantharaj Ethirajulu、Jeanette M. Wood、Brian W. Dymock

  DOI：10.1021/jm201454n

  日期：2012.3.22

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.